Practical Guide to Toxicology and Human Health Risk Assessment

LAURA ROBINSON, MSc, has worked as a toxicologist both in industry and in consultancy for over ten years. She has extensive experience in chemical risk assessments, occupational exposure issues, assessment and interpretation of toxicological data. She is a qualified teacher and has designed and delivered numerous training courses and written two books.

• Foreword xxiPreface xxiiiAcknowledgment xxv1 Welcome to the World of Toxicology 11.1 Chemicals – They Are All Around Us 11.2 Synthetic or Naturally Occurring Chemicals – Which Are “Safer”? 11.3 Chemical Control Regulations 21.4 Perception of Chemical Risk 31.5 Why Is Toxicology Important? 41.6 Summary 42 Basic Toxicological Terminology 52.1 The Cell 52.1.1 Stem Cells, Somatic Cells, and Germ Cells 52.2 Homeostasis72.3 Adaptation and Cell Injury 72.4 Cellular Responses to Injury 72.5 Mode of Action and Mechanism of Action 92.6 Adverse Effects 92.7 Biological and Statistical Significance 102.8 Local and Systemic Effects 112.9 How Chemicals Cause Harm 112.10 Acute and Chronic Exposures 122.11 Chemical Interactions in Mixtures 142.12 Summary 153 The Dose Makes the Poison 193.1 Dose– Response and Dose–Effect Relationships 193.2 Internal and External/Exposure Dose 203.3 The Dose Makes the Poison: Dose–Response/Effect Curves 213.4 No Observed Adverse Effect Level (NOAEL) 233.5 Lowest Observed Adverse Effect Level (LOAEL) 243.6 What Affects the NOAEL and LOAEL? 243.7 No Observed Effect Level (NOEL) 243.8 Summary 244 Toxicokinetics 274.1 Why Is Toxicokinetics So Useful? 284.2 ADME: Absorption, Distribution, Metabolism, and Excretion 294.3 Biotransformation (Metabolism) 364.4 Bioavailability and Area Under the Curve (AUC) 384.5 Assessment Approaches 394.6 Summary 405 Factors That Modify Toxicity 455.1 Lifestyle Factors – Alcohol and Tobacco 455.2 Influence of Age 465.3 Health Status 465.4 Nutritional Status – Diet 475.5 Sex 485.6 Adaptation 485.7 Genetic Variability 485.8 Summary 496 Local Effects 536.1 Irritants and Corrosives 536.2 Skin Structure 546.3 Irritant Contact Dermatitis 566.4 Chemical Corrosives 606.5 The Skin as a Target Organ – Severity of Effect 606.6 Chemical Irritants and Other Exposure Routes 616.7 Summary 627 Systemic Effects 657.1 Chemical Allergies 667.2 Genetic Toxicology 797.3 Carcinogenicity 917.4 Reproductive and Developmental Toxicology 1007.4.10 Maternal Mediated Toxicity 1198 Target Organ Toxicity 1238.1 The Liver 1248.2 The Kidney 1398.3 The Immune System 1518.4 Hematopoietic System and Blood 1678.5 The Nervous System 1768.6 The Respiratory Tract 1968.7 The Endocrine System 2089 Assessment Methods 2279.1 Assessment of Irritation and Corrosive Effects 2289.2 Assessment of Acute Toxicity 2399.3 Repeated9.4 Assessment of Carcinogenicity 2599.5 Assessment of Genetic Toxicity 2679.6 Assessment of Reproductive and Developmental Effects 2839.7 Assessment of Skin and Respiratory Sensitization 29510 Alternative Methods to Animal Testing 30710.1 The Drive for Alternative Methods 30710.1.1 A Different Approach? 30810.3 In Vitro and Ex Vivo Methods 30810.4 Twenty‐ First Century Toxicity Testing 31010.5 Physicochemical Data and Their Use in Hazard Identification and Exposure Assessment 31410.6 Summary 31711 Human Health Risk Assessment 32111.1 Human Health Risk Assessments – Prospective and Retrospective 32111.2 Risk, Hazard, and Exposure 32211.3 Chemical Risk Assessments 32311.4 Linear Dose Response – Nonthresholded Effects 33311.5 Exposure Assessment 33611.6 Risk Characterization – Do We Have a Problem? 34011.7 Summary 341Glossary 345Index 355